This invention relates to systems and methods for micro-invasive, continuous monitoring of a patient""s changes in blood density and hematocrit in order to determine the blood volume and microvascular pooling of the patient over time to better profile the patient""s response to hemodialysis, trauma, or bum injury and to achieve more effective diagnosis and treatment.
An apparatus and method are described to monitor the time of sound transmission in the blood stream of a patient, to use a linear relationship between compressibility and density for accurate and sensitive assessment of blood density changes, and to employ optical density for assessment of hematocrit changes due to dilution by saline, dialysate or therapeutic changes. Through appropriate clinical protocols, the density and hematocrit changes are used individually or in combined form to determine the plasma protein concentration, blood volume, change in blood volume, and microvascular pooling of the patient over time.
Hypotension and hypovolemia are common circulatory problems that occur during shock (Chien et al, American Journal of Physiology, 210:1411-1418), traumatic injury, dialysis (Amerling et al in Clinical Dialysis 3rd Edition, Appleton and Lang editors, 1995) and surgical interventions. A variety of disorders and injuries are related to the occurrence of hypotension (Daugirdas, Kidney International 39:233-246). Fluid loss related to burn injury or hemorrhage due to trauma is examples of situations where compensation for such loss is necessary. Infusing isotonic saline, plasma or other physiological solutions into the circulation until arterial pressure is elevated to normal is usually employed as the treatment. Although blood volume reduction correlates with reduction in arterial pressure under laboratory simulations of injury and anesthesia, actual occurrences of traumatic blood loss often show only slightly reduced arterial pressures due to the body""s neural compensation mechanisms. Once these mechanisms reach their limits, arterial pressure can drop rapidly. The management of this subnormal arterial pressure is critical to survival; immediate restoration of arterial pressure after traumatic injury can cause more problems than allowing the pressure to remain subnormal. Rapid restoration of arterial pressure results in higher oxygen demand and the increase in blood flow may dislodge clots to cause stroke.
While the body""s compensation mechanisms are important to survival, limitations exist in the ability to determine several factors including the volume of blood loss, the distribution of blood volume between the microcirculation and macrocirculation, the necessary volume for infusion, and whether overexpansion of the blood volume has occurred after infusion. Arterial pressure monitoring is unable to provide sufficient information to address these concerns. A need exists for precise monitoring of changes to blood volume and microvascular pooling in patients, particularly over extended time periods.
Beyond trauma and burn injury, a number of medical conditions require such precise monitoring of blood volume. Invasive surgery and dialysis are two common situations where monitoring blood volume changes provide important information related to the outcome of the surgery and dialysis. For example, about 30% of patients undergoing dialysis in the United States will experience hypotension and, occasionally, circulatory shock. Milder symptoms include muscle cramping and lightheadedness. These dialysis related side effects are implicated in reduced dialysis efficacy.
Dialysis and systems for dialysis are well known in the art. These work by extracting a significant fraction of fluid from the circulating blood. Compensation for this reduction in blood volume normally occurs through fluid restituted from the tissue. The activation of the microcirculation by hemodialysis leads to pooling of blood in the microcirculation affecting a low venous return, poor cardiac filling, lowered cardiac output and then hypotension. For patients undergoing a well-controlled fluid removal, these cardiovascular changes and hypovolemia are the reason for hypotension development during the course of hemodialysis. Using saline or dialysate dilution, we can monitor the change in blood volume over times, for example every half hour. A continuous change in blood density can be analyzed and microvascular pooling within the circulation can be determined. These parameters can be used by physicians to carefully monitor the cardiovascular changes that are responsible for the development of hypotension in dialysis patients.
When patients undergo hemodialysis or are subject to trauma or bums, there is significant exchange of fluid and protein between the tissue and blood compartment. These exchanges will alter the plasma protein concentration. Consequently an on-line system capable of monitoring changes in plasma protein concentration will be valuable to the physician in selecting an appropriate fluid therapy to compensate for the loss of plasma and/or plasma protein. Currently no system can assess on-line and clinically monitor plasma protein concentration.
The use of sound velocity measurements in blood to assess blood volume has been attempted and described previously. Krivitski, in U.S. Pat. Nos. 5,453,576 and 5,685,989 describes an apparatus and method for measuring several hemodynamic parameters by using a sound velocity sensor. The information contained in the ""576 and the ""989 patent is incorporated by reference as though cited in its entirety. The technique described uses a linear approximation of a non-linear relationship between the sound velocity and the density of the blood. This approximation introduces additional error into the volume computation, which limits the accuracy of the system. Further, the ""576 patent is limited to large variations in sound velocity which make it inaccurate to assess blood volume.
The system patented by Schneditz in U.S. Pat. No. 5,830,365 also utilizes sound velocity for the measurement of total protein concentration, and then the blood volume by altering the dialyzer to run at a different ultrafiltrate extraction rate. These two methods are limited to large variations in sound velocity and the requirement of no blood pooling to the microcirculation.
Several other devices exist which are used to monitor blood volume or blood parameter changes. These include the Know-Recirc(trademark) hematocrit measurement device produced by HandH Control Systems (Jackson, Miss.) and described in U.S. Pat. No. 5,312,550 and an optical device marketed under the Crit-Line(copyright) platform and the Transcutaneous Access Flow device by HemaMetrics Corporation (Boston, Mass.) described in U.S. Pat. Nos. 5,499,627 and 6,117,099. These devices continuously monitor the change in hematocrit over a dialysis session. Increases in hematocrit over the session are interpreted as a decrease in plasma volume thereby theoretically providing a mechanism for monitoring blood volume changes. This method does not account for the Fahraeus effect where microvascular pooling of blood can result in an increase in hematocrit. By not correcting for microvascular pooling, blood volume changes estimated by this device are off by a factor of two or more. Again, sensitivity of this device is limited and can cause incorrect diagnoses or treatments. Daugirdas (American J. Kidney Disease, 38:S11-S17, 2001) commented that none of these hematocrit approaches are successful because the conclusion from the measured hematocrits exhibits considerable interpatient and intrapatient variability. A similar problem exists in the work of Polaschegg in U.S. Pat. No. 5,230,341. Correction for microvascular pooling and sensitivity are deficient in the ""341 patent and incorrect results on the projected blood volume occur leading to potentially harmful treatments.
The present invention provides a method and an optical/ultrasound probe to accurately and reliably determine compressibility, density, hematocrit, and plasma protein concentration, and the changes of these blood parameters due to the infusion of saline or dialysate for the quantification of blood volume or microvascular pooling in patients. The invention utilizes the changes of blood density and hematocrit over time while accounting for the effect of the microcirculation to provide medical professionals with valuable information on microvascular pooling and hypovolemia for the prevention of complications related to trauma and hemodialysis.
Further, the present invention measures through the ultrasound probe and a signal processing unit the phase shift between emitting ultrasound and receiving ultrasound, converts the phase shift to transmssion time and subsequently to sound velocity of blood flowing in a corporeal or extracorporeal system, and uses the linear relationship between compressibility and density to calculate from sound velocity the compressibility and density of blood.
The novel embodiments of the optical ultrasound probe provide significant advantages over the prior art. These include:
(1) A simpler hardware and software to detect phase shift of ultrasound signals for the determination of sound velocity;
(2) A factory procedure to calibrate the relationship between the sound velocity and density of blood on using the ultrasound probe to determine density;
(3) A set of computer files and equations to account for the dependence of density and sound velocity of blood on temperature;
(4) An on-line method using the ultrasound probe to calibrate the optical density of the optical probe for the determination of hematocrit;
(5) The combined use of the hematocrit and density measurement for the determination of plasma protein concentration;
(6) A data averaging procedure to better define the time course of density, hematocrit, and plasma protein concentration and to better characterize the interrelation between hematocrit and density changes;
(7) A graphic organization of the hematocrit and density measurements to differentiate whether a therapeutic process induces the patient to produce hypovolemia, microvascular pooling or both;
(8) An on-line analysis and procedure to quantify the time course of microvascular pooling, blood volume, and plasma protein concentration.
The combination of these eight features enables the optical/ultrasound probe to be produced at low cost, to achieve accurate assessments and to provide crucial information for the physician to select an effective strategy to prevent or treat hypotension in any patient.
Blood is a mixture of cells and plasma. The density and compressibility of blood is the sum of its components weighted by the volume fraction. The velocity of ultrasound in blood is related to a variety of factors, including the hematocrit, blood and plasma density, plasma protein concentration, and total protein concentration of blood. Likewise, blood compressibility also relates to these physical parameters of blood and plasma. These relationships are difficult to identify because of a lack of accurate measurement systems. Attempts at relating variable factors have deduced approximations to be utilized by the system described in the ""576 patent and in the Know-Recirc(trademark) and the Crit-Line(copyright) hematocrit measurement system. These empirical approximations limit the accuracy of the measurement systems and introduce errors into the data analysis.
The more accurate calculation of blood volume and the determination of its distributions within the circulation taught herein are used to monitor and treat patients more effectively. Software and hardware are configured to generate and receive the ultrasound wave and light and use the information to monitor the changes in plasma protein concentration and redistribution of blood volume in patients. Methods for interfacing the data generated by the monitoring technique on the transmission of sound, absorption and reflection of light with analytical machinery will become apparent to those of skill in the art based on the description contained herein.